European Medicines Agency has issued a new guidelines describing stability testing requirements for variations to a marketing authorisation after approval, setting out the differing requirements for changes to active pharmaceutical ingredients (API) and finished dosage form production.
Manufacturers in the EU making changes to their manufacturing processes will have to submit additional stability data, according to these new guidelines.
What is a Variation…?
Variation regulations and guidelines
Types of variations
Type-IA
Type-IB
Type-II
Extension
Unforeseen variations (Z category)
Grouping of variations
Work sharing of variations
Fee
eAF
Renewals
What is a Variation…?
Variation regulations and guidelines
Types of variations
Type-IA
Type-IB
Type-II
Extension
Unforeseen variations (Z category)
Grouping of variations
Work sharing of variations
Fee
eAF
Renewals
PIC/S is a combine term used for the execution of activities of Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme
harmonize, educate, and update aspects relating to Good Manufacturing Practice among member countries
harmonized relation among regulatory authorities and governments
members
history
role
objective and function
guidlines
Pharmaceutical development report (pdr)Atul Bhombe
pharmaceutical development report PDR is the one of the significant document of CTD (common technical document) which requires for in approval of new drug process
plasma master file in European countries and requirements in letter of intent...Sanjay batra
it includes that what is plasma master file, principles, procedure to file PMF, strategy involved, administration information, certification procedure & inspection
ICH stability guidances provide guidance for new drug substances and drug products .CDER now wishes to apply these recommendations to ANDAs. Specific recommendations were given in FDA “Guidance for Industry: ANDAs: Stability Testing of Drug Substances and Products. Recently FDA issued “Guidance for Industry: ANDAs: Stability Testing of Drug Substances and Products: Questions and Answers.
Drug Regulations has prepared a presentation on ANDA stability requirements.
The dissolution test is an important means of assuring the continuing performance of non-solution orally administered drug products. The development of a dissolution test procedure is briefly discussed in USP general information chapter In Vitro and In Vivo Evaluation of Dosage Forms 1088, whereas general information chapter Validation of Compendial Procedures 1225 gives limited validation information for dissolution testing. Neither of these two chapters provides a level of detail and focus sufficient for dissolution testing. In 2001, a Stimuli article provided an initial rationale and discussion of content for a new general information chapter. The new chapter, The Dissolution Procedure: Development and Validation 1092, was intended to supplement the information in 1088 and 1225 and provided step-by-step detail for development and validation as well as offering information on new technology and equipment. In 2006, the chapter became official with the Second Supplement to USP 29–NF 24 (2–4).
The General Chapters—Dosage Forms Expert Committee 2010–2015 placed the review and possible revision of The Dissolution Procedure: Development and Validation 1092 on its work plan for the 2010–2015 revision cycle (2011) .
Drug Regulations has prepared this presentation based on the proposed chapter.
PIC/S is a combine term used for the execution of activities of Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme
harmonize, educate, and update aspects relating to Good Manufacturing Practice among member countries
harmonized relation among regulatory authorities and governments
members
history
role
objective and function
guidlines
Pharmaceutical development report (pdr)Atul Bhombe
pharmaceutical development report PDR is the one of the significant document of CTD (common technical document) which requires for in approval of new drug process
plasma master file in European countries and requirements in letter of intent...Sanjay batra
it includes that what is plasma master file, principles, procedure to file PMF, strategy involved, administration information, certification procedure & inspection
ICH stability guidances provide guidance for new drug substances and drug products .CDER now wishes to apply these recommendations to ANDAs. Specific recommendations were given in FDA “Guidance for Industry: ANDAs: Stability Testing of Drug Substances and Products. Recently FDA issued “Guidance for Industry: ANDAs: Stability Testing of Drug Substances and Products: Questions and Answers.
Drug Regulations has prepared a presentation on ANDA stability requirements.
The dissolution test is an important means of assuring the continuing performance of non-solution orally administered drug products. The development of a dissolution test procedure is briefly discussed in USP general information chapter In Vitro and In Vivo Evaluation of Dosage Forms 1088, whereas general information chapter Validation of Compendial Procedures 1225 gives limited validation information for dissolution testing. Neither of these two chapters provides a level of detail and focus sufficient for dissolution testing. In 2001, a Stimuli article provided an initial rationale and discussion of content for a new general information chapter. The new chapter, The Dissolution Procedure: Development and Validation 1092, was intended to supplement the information in 1088 and 1225 and provided step-by-step detail for development and validation as well as offering information on new technology and equipment. In 2006, the chapter became official with the Second Supplement to USP 29–NF 24 (2–4).
The General Chapters—Dosage Forms Expert Committee 2010–2015 placed the review and possible revision of The Dissolution Procedure: Development and Validation 1092 on its work plan for the 2010–2015 revision cycle (2011) .
Drug Regulations has prepared this presentation based on the proposed chapter.
This presentation will address Refuse to Receive standards when Submitting ANDAs and Prior approval supplements (PASs) to ANDAs. The presentation highlights deficiencies that may cause FDA to refuse-to-receive an ANDA.
This presentation is compiled by “ Drug Regulations” from freely available resources like the FDA on the World wide web.
“Drug Regulations” is a non profit organization which provides free online resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest information from the world of Pharmaceuticals.
The presentation will give an insight into ICH Q1A Stability testing of New drug products. Here the ppt is much focused on stability requirements for ANDA, no: of batches, storage conditions, testing frequency.
Medicinal products must comply with their approved specifications before they are released into the market. Compliance with release specifications can be demonstrated by performing a complete set of tests on the active substance and/or finished product, according to the approved specifications. Under certain conditions, an alternative strategy to systematic end product testing is possible. So far this concept has been mainly applied to sterility testing of terminally sterilised products and has become associated with parametric release applications. Recent guidelines adopted in the ICH context (ICH Q8, Q9 and Q10) have made it possible to apply a similar release decision process to tests other than sterility, this approach has been called Real Time Release Testing (RTRT).
RTRT is a system of release that gives assurance that the product is of intended quality, based on the information collected during the manufacturing process, through product knowledge and on process understanding and control. RTRT recognises that under specific circumstances an appropriate combination of process controls (critical process parameters) together with pre-defined material attributes may provide greater assurance of product quality than end-product testing and the context as such be an integral part of the control strategy. The RTRT principle is already authorised for use as an optional alternative to routine sterility testing of products terminally sterilised in their final container i.e. parametric release. Enhanced product knowledge and process understanding, the use of quality risk management principles and the application of an appropriate pharmaceutical quality system, as defined within ICH Q8,Q9 and Q10 provide the platform for establishing RTRT mechanisms for other applications, for new products as well as established marketed products. Release of a product can be a combination of a RTR approach for certain critical quality attributes (CQAs) and a more conventional evaluation for other CQAs (partial RTR).
This presentation deals with the concepts of Real Time Release Testing. This presentation was compiled from material freely available from FDA , ICH , EMEA and other free resources on the world wide web.
This presentation describes the principles of qualification and validation which are applicable to the facilities, equipment, utilities and processes used for the manufacture of medicinal products. It is a GMP requirement that manufacturer’s control the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process. Any planned changes to the facilities, equipment, utilities and processes, which may affect the quality of the product, should be formally documented and the impact on the validated status or control strategy assessed.
This presentation gives a overview of the new FDA draft guidance on Analytical Method Validation and compares it with the older version issued in the year 2000.
Quality Assurance is of Tremendous Importance in Pharma and Health care sector.
A brief of that is try to explain here..
A Trust of the Customer on Product is solely based on the Effective QA
ATUL CHAUDHARY (STUDENTS)
DEPARTMENT OF PHARMACEUTICS
ISF COLLEGE OF PHARMACY, GHALKALAN, MOGA , PUNJAB
THIS SLIDE IS THE BEST SLIDE FOR PREPARING THE TOPIC SUPAC OF REGULATORY AFFAIRS SUBJECT
SLIDE ARE SPECIALLY DESIGN FOR MASTER STUDENTS AS WELL AS GRADUATION STUDENTS
This presentation highlights the reasons which lead to the withdrawal of the 2002 Guidance of the FDA and the current issue with Blend Uniformity and Content Uniformity Determinations.
WHO has recently issued draft document titled "Guidelines on Validation". These guidelines (i.e., the main text included in this working document) cover the general principles of validation and qualification.
These guidelines focus mainly on the overall concept of validation and are not intended to be prescriptive in specific validation requirements. This document serves as general guidance only and the principles may be considered useful in its application in the manufacture and control of starting materials and finished pharmaceutical products (FPPs), as well as other areas. Validation of specific processes and systems, for example, in sterile product manufacture, requires much more consideration and a detailed approach that is beyond the scope of this document. The general text in this document may be applicable to validation and qualification of premises, equipment, utilities, systems, processes, and procedures.
The draft on the specific topics, the appendices to this main text, will follow. The following is an overview on the appendices that are intended to complement the text of this working document:
Appendix 1: Validation of heating, ventilation and air-conditioning systems - will be replaced by cross reference to WHO Guidelines on GMP for HVAC systems for considerations in qualification of HVAC systems (update - working document QAS/15.639/Rev. 1)
Appendix 2: Validation of water systems for pharmaceutical use - will be replaced by cross-reference to WHO Guidelines on water for pharmaceutical use for consideration in qualification of water purification systems
Appendix 3: Cleaning validation - consensus to retain
Appendix 4: Analytical method validation - update in process
Appendix 5: Validation of computerized systems - update in process
Appendix 6: Qualification of systems and equipment - update in process
Appendix 7: Non-sterile process validation - update already published as Annex 3, WHO Technical Report Series, No. 992, 2015
Comments on this draft document are due by July 12, 2016.
A presentation on this guidance is given below:
Presentation on New WHO Guidance on Validations
Environmental Monitoring describes the microbiological testing under- taken in order to detect changing trends of microbial counts and micro- flora growth within cleanroom or controlled environments. The results obtained provide information about the physical construction of the room, the performance of the Heating, Ventilation, and Air-Conditioning (HVAC) system, personnel cleanliness, gowning practices, the equipment, and cleaning operations.
Over the past decade, environmental monitoring has become more sophisticated in moving from random sampling, using an imaginary grid over the room and testing in each grid, to the current focus on risk assessment and the use of risk assessment tools to determine the most appropriate methods for environmental monitoring.
This presentation gives current trends in the application of risk assessment to the practice of environmental monitoring.
This presentation is compiled from freely available resources like the websites of FDA, EMA ,WHO and research papers published by experts in this field like Sandle, T Reinmüller, B , Hyde, W,, Costello, E.K., Lauber, C. L., Hamady, M., Fierer, N., Gordon, J.I., Knight, R.
Paper published by T. Sandle on clean room contamination was referred extensively for this presentation. “Drug Regulations” is a non profit organization which provides free online resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest information from the world of Pharmaceuticals.
This presentation gives an overview of : Validation of microbiological methods , Considering some of the limitations and
Key criteria that may be applicable for assessment.
More from GMP EDUCATION : Not for Profit Organization (20)
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stockrebeccabio
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stock
Telegram: bmksupplier
signal: +85264872720
threema: TUD4A6YC
You can contact me on Telegram or Threema
Communicate promptly and reply
Free of customs clearance, Double Clearance 100% pass delivery to USA, Canada, Spain, Germany, Netherland, Poland, Italy, Sweden, UK, Czech Republic, Australia, Mexico, Russia, Ukraine, Kazakhstan.Door to door service
Hot Selling Organic intermediates
1. This presentation is compiled by “ Drug Regulations” a
non profit organization which provides free online
resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
4/16/2014 1
2. This presentation is compiled from freely
available resources like the website of EMA
specifically “Guideline on stability testing for
applications for variations to a marketing
authorisation”
“Drug Regulations” is a non profit organization
which provides free online resource to the
Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
4/16/2014 2
Drug Regulations : Online
Resource for Latest Information
3. ◦ Variations
Require generation of stability data
On the finished product or the active substance
Continue the stability studies required, including commitment
batches, up to the approved shelf-life / retest period
Inform authorities immediately if any problems with the stability
e.g. if outside specification or potentially outside specification.
4/16/2014 3Drug Regulations : Online Resource for Latest Information
4. ◦ Base the stability studies on the knowledge and experience acquired of the
active substances and finished products.
◦ The available information must be taken into account such as:
◦ a) For active substances:
the stability profile including the results of stress testing, if applicable
(except herbals);
the supportive data;
the primary data of long term and accelerated testing.
◦ b) For finished products:
the supportive data;
the primary data of long term and accelerated testing.
4/16/2014 4Drug Regulations : Online Resource for Latest Information
5. ◦ Assess whether the intended change has the
potential to impact the
quality characteristics
stability
of the active substances and/or
the finished products
4/16/2014 5Drug Regulations : Online Resource for Latest Information
6. When stability data are required, the choice of test
conditions, refers to
◦ CHMP/ICH Guideline on Stability Testing of New Drug Substances
and Products,
◦ CHMP/QWP Guideline on Stability Testing of Existing Active
Substances and Related Finished Products,
◦ The CVMP/VICH Guideline on Stability Testing of New Veterinary
Drug Substances and Medicinal Products
◦ The CVMP/QWP Note for Guidance on Stability Testing of Existing
Active Substances and Related Finished Products, respectively.
4/16/2014 6Drug Regulations : Online Resource for Latest Information
7. Type I variations
If a variation to a marketing authorisation fulfils the conditions defined in the
Commission Regulation (EC) No 1234/2008 for Type IA variations, and if
stability data are required, the minimum set of data to be submitted with the
variation is defined in the Guidelines on the details of the various categories
of variations, on the operation of the procedures laid down in Chapters II, IIa,
III and IV of Commission Regulation (EC) No 1234/2008 of 24 November
2008 concerning the examination of variations to the terms of marketing
authorisations for medicinal products for human use and veterinary
medicinal products and on the documentation to be submitted pursuant to
those procedures.
4/16/2014 7Drug Regulations : Online Resource for Latest Information
8. Type I variations
A Type IB variation is the default category under the Commission Regulation (EC) No
1234/2008.
The associated classification guideline provides examples of different types of Type IB
changes that have been included in the guideline with recommended documentation.
Where a change may impact stability, the required stability data at the time of
submission are specified in the guideline.
In other Type IB by default changes, which are not specifically described in the
classification guideline, the required stability data has to be decided on a case by case
basis.
However, consideration should be given to specified requirements for any other similar
changes which have actually been included as examples in the guideline.
4/16/2014 8Drug Regulations : Online Resource for Latest Information
9. Type II variations
The Commission Regulation (EC) No 1234/2008 defines Type II variations as major variations which
may have a significant impact on the quality, safety or efficacy of medicinal products.
Type II variations are defined in the Guidelines on the details of the various categories of variations, on
the operation of the procedures laid down in Chapters II, IIa, III and IV of the Commission Regulation
(EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of
marketing authorisations for medicinal products for human use and veterinary medicinal products and
on the documentation to be submitted pursuant to those procedures.
However, data to be submitted with these variations are not defined in the majority of cases.
The following Type II variations refer to specific Type II variations as outlined in the Guidelines
mentioned above.
The stability data outlined below should to be part of the documentation at submission of the
variation.
4/16/2014 9Drug Regulations : Online Resource for Latest Information
10. 4/16/2014 10
Type II Variation . (B.I.a.1.b)
Change Requirement
• Change in the manufacturer of a starting material /
reagent / intermediate used in the manufacturing
process of the active substance
or
• change in the manufacturer (including where relevant
quality control testing sites) of the active substance,
where no
• Ph. Eur. certificate of suitability is part of the approved
dossier: Introduction of a manufacturer of active
substance supported by an ASMF
In case of an introduction of a manufacturer of the active
substance that is supported by an ASMF stability data
should be included in the applicants part of the ASMF.
In relation to stability data, of the active substance, the
recommendations given in the guideline on stability
testing of existing active substances and finished
products should be utilised.
If the quality characteristics/impurity profile of the active
substance are changed in a way that may impact the
stability of the finished product, additional stability data
on the finished product, in long term and accelerated*
conditions, six months data on at least two batches of at
least pilot scale batch size are recommended.
11. 4/16/2014 11
Type II Variation . (B.I.a.1.c)
Change Requirement
• Change in the manufacturer of a starting material /
reagent / intermediate used in the manufacturing
process of the active substance
• or
• change in the manufacturer (including where relevant
quality control testing sites) of the active substance,
where no Ph. Eur. certificate of suitability is part of the
approved dossier:
• The proposed manufacturer uses a substantially
different route of synthesis or manufacturing
conditions, which may have a potential to change
important quality characteristics of the active
substance, such as qualitative and/or quantitative
impurity profile requiring qualification, or physico-
chemical properties impacting on bioavailability
In relation to stability data of the active substance, the
recommendations given in the guideline on stability
testing of existing active substances and finished
products should be utilised..
If the quality characteristics of the active substance are
changed in a way that may impact the stability of the
finished product, additional stability data on the finished
product, in long term and accelerated* testing
conditions, six months data on at least two batches of at
least pilot scale batch size are recommended.
12. 4/16/2014 12
Type II Variation . (B.I.a.1.g)
Change Requirement
• Change in the manufacturer of a starting material /
reagent / intermediate used in the manufacturing
process of the active substance
• or
• Change in the manufacturer (including where relevant
quality control testing sites) of the active substance,
where no Ph. Eur. certificate of suitability is part of the
approved dossier:
• Introduction of a new manufacturer of the active
substance that is not supported by an ASMF and
requires significant update to the relevant active
substance section of the dossier
In relation to stability data of the active substance, the
recommendations given in the guideline on stability
testing of existing active substances and finished
products should be utilised.
If the quality characteristics of the active substance are
changed in a way that may impact the stability of the
finished product, additional stability data on the finished
product, in long term and accelerated* testing
conditions, six months data on at least two batches of at
least pilot scale batch size are recommended.
13. 4/16/2014 13
Type II Variation . (B.I.a.2.b)
Change Requirement
• Changes in the manufacturing process of the active
substance:
• Substantial changes to the manufacturing process of
the active substance which may have a significant
impact on the quality, safety or efficacy of the
medicinal product
In variations to the manufacturing process of the active
substance, the following approaches may be considered
as acceptable:
If the quality characteristics (e.g. physical characteristics,
impurity profile) of the active substance are changed in a
way that stability may be compromised, comparative
stability data are recommended in long term and
accelerated* testing conditions, on the active substance
before and after the change:
• for active substances known to be stable: three
months data on at least one batch of at least pilot
scale batch size (see Annex I for the definition of
stable active substance).
14. 4/16/2014 14
Type II Variation . (B.I.a.2.b)
Change Requirement
• Changes in the manufacturing process of the active
substance:
• Substantial changes to the manufacturing process of
the active substance which may have a significant
impact on the quality, safety or efficacy of the
medicinal product
• for active substances known to be unstable: six
months data on at least three batches of at least pilot
scale batch size.
If the quality characteristics of the active substance are
changed in a way that may impact the stability of the
finished product, additional stability data on the finished
product, in long term and accelerated* testing
conditions, six months data on at least two batches of at
least pilot scale batch size are recommended.
15. 4/16/2014 15
Type II Variation . (B.I.a.2.d)
Change Requirement
• Changes in the manufacturing process of the active
substance:
• The change relates to a herbal medicinal product and
there is a change to any of the following: geographical
source, manufacturing route or production
In variations to the manufacturing process of the active
substance, the following approaches may be considered
as acceptable:
If the quality characteristics (e.g. physical characteristics,
impurity profile) of the active substance are changed in a
way that stability may be compromised, comparative
stability data are recommended in long term and
accelerated* term testing conditions, on the active
substance before and after the change:
• for active substances known to be stable: three
months data on at least one batch of at least pilot
scale batch size (see Annex I for the definition of
stable active substance).
• for active substances known to be unstable: six
months data on at least three batches of at least pilot
scale batch size.
16. 4/16/2014 16
Type II Variation . (B.I.a.2.d)
Change Requirement
• Changes in the manufacturing process of the active
substance:
• The change relates to a herbal medicinal product and
there is a change to any of the following: geographical
source, manufacturing route or production
If the quality characteristics of the active substance are
changed in a way that may impact the stability of the
finished product, additional stability data on the finished
product, in long term and accelerated* testing
conditions, six months data on at least two batches of at
least pilot scale batch size are recommended.
17. 4/16/2014 17
Type II Variation . (B.I.c.1.b)
Change Requirement
• Change in immediate packaging of the active
substance:
• Qualitative and/or quantitative composition for sterile
and non-frozen biological/immunological active
substances
In case of a change to the immediate packaging of a
sterile active substance the following approach may be
considered as acceptable:
Comparative stability data are required using long term
and accelerated* testing conditions of six months in
duration on at least 2 batches of at least pilot scale of
the active substance.
(Note: According to the scope this guideline is not
applicable to biological/immunological active
substances).
18. 4/16/2014 18
Type II Variation . (B.II.a.3.b.2)
Change Requirement
• Change in composition (excipients) of the finished
product:
• Qualitative or quantitative changes in one or more
excipients that may have a significant impact on the
safety, quality or efficacy of the medicinal product.
In case of a change in the composition of the finished
product, the following approaches may be considered as
acceptable:
For conventional dosage forms (e.g. conventional release
solid dosage form, solutions) and when the active
substance is known to be stable, comparative stability
data, 6 months in duration, long term and accelerated*
testing conditions on at least two batches of at least
pilot scale are recommended.
For critical dosage forms (e.g. modified release form) or
when the active substance is known to be unstable,
comparative stability data 6 months in duration, long
term and accelerated* stability testing conditions on at
least three primary batches are recommended. Two of
three batches should be at least pilot scale; the third
batch may be smaller.
19. 4/16/2014 19
Type II Variation . (B.II.a.4.b)
Change Requirement
• Change in coating weight of oral dosage forms or
change in weight of capsule shells:
• Gastro-resistant, modified or prolonged release
pharmaceutical forms where the coating is a critical
factor for the release mechanism
In variations to the coating weight of oral dosage forms,
the following approach may be considered as acceptable:
• Comparative stability data, 6 months in duration, long
term and accelerated* stability testing conditions on at
least three primary batches are recommended. Two of
three batches should be at least pilot scale; the third
batch may be smaller.
20. 4/16/2014 20
Type II Variation . (B.II.a.5.)
Change Requirement
• Change in concentration of a single-dose, total use
parenteral product, where the amount of the active
substance per unit dose (i.e. the strength) remains the
same
In variations in concentration of single-dose, total use
parenteral product, the following approaches may be
considered as acceptable:
• Comparative stability data, 6 months in duration, long
term and accelerated* stability testing conditions on at
least three primary batches are recommended. Two of
three batches should be at least pilot scale; the third
batch may be smaller.
21. 4/16/2014 21
Type II Variation . (B.II.b.1.c)
Change Requirement
• Replacement or addition of a manufacturing site for
part or all of the manufacturing process of the
finished product: Site where any manufacturing
operation(s) take place, except batch release, batch
control, and secondary packaging, for
biological/immunological medicinal products, or for
pharmaceutical forms manufactured by complex
manufacturing processes
In variations (replacement or addition) to a
manufacturing site for part or all of the manufacturing
process of the finished product, the following
approaches may be considered as acceptable:
• If the quality characteristics (e.g. physical
characteristics, impurity profile) of the finished
product are changed in a way that stability may be
compromised, comparative stability data are
recommended in long term and accelerated* testing
conditions, on the finished product before and after
the change:
22. 4/16/2014 22
Type II Variation . (B.II.b.1.c)
Change Requirement
• Replacement or addition of a manufacturing site for
part or all of the manufacturing process of the
finished product: Site where any manufacturing
operation(s) take place, except batch release, batch
control, and secondary packaging, for
biological/immunological medicinal products, or for
pharmaceutical forms manufactured by complex
manufacturing processes
For conventional dosage forms (e.g. conventional release
solid dosage form, solutions) and when the active
substance is known to be stable, comparative stability
data, 6 months in duration, long term and accelerated*
testing conditions on at least two batches of at least
pilot scale are recommended.
For critical dosage forms (e.g. modified release form) or
when the active substance is known to be unstable,
comparative stability data, 6 months in duration, long
term and accelerated* stability testing conditions on at
least three primary batches are recommended. Two of
three batches should be at least pilot scale; the third
batch may be smaller.
(Note: According to the scope this guideline is not
applicable to biological/immunological active substances
and related finished products).
23. 4/16/2014 23
Type II Variation . (B.II.b.3.b)
Change Requirement
• Change in the manufacturing process of the finished
product, including an intermediate used in the
manufacture of the finished product:
• Substantial changes to a manufacturing process that
may have a significant impact on the quality, safety
and efficacy of the medicinal product
In variations to the manufacturing process of the
finished product, the following approaches may be
considered as acceptable:
If the quality characteristics (e.g. physical characteristics,
impurity profile) of the finished product are changed in a
way that stability may be compromised, comparative
stability data are recommended in long term and
accelerated* testing conditions, on the finished product
before and after the change:
For conventional dosage forms (e.g. conventional release
solid dosage form, solutions) and when the active
substance is known to be stable, comparative stability
data, 6 months in duration, long term and accelerated*
testing conditions on at least two batches of at least
pilot scale are recommended.
24. 4/16/2014 24
Type II Variation . (B.II.b.3.b)
Change Requirement
• Change in the manufacturing process of the finished
product, including an intermediate used in the
manufacture of the finished product:
• Substantial changes to a manufacturing process that
may have a significant impact on the quality, safety
and efficacy of the medicinal product
For critical dosage forms (e.g. modified release form) or
when the active substance is known to be unstable,
comparative stability data, 6 months in duration, long
term and accelerated* stability testing conditions on at
least three primary batches are recommended. Two of
three batches should be at least pilot scale; the third
batch may be smaller.
25. 4/16/2014 25
Type II Variation . (B.II.b.3.d)
Change Requirement
• Change in the manufacturing process of the finished
product, including an intermediate used in the
manufacture of the finished product: Introduction of a
non-standard terminal sterilisation method
In variations to the manufacturing process of the
finished product, the following approaches may be
considered as acceptable:
If the quality characteristics (e.g., impurity profile) of the
finished product are changed in a way that stability may
be compromised, comparative stability data are
recommended in long term and accelerated* testing
conditions, on the finished product before and after the
change:
For conventional dosage forms (e.g. solutions) and when
the active substance is known to be stable, comparative
stability data, 6 months in duration, long term and
accelerated* testing conditions on at least two batches
of at least pilot scale are recommended.
26. 4/16/2014 26
Type II Variation . (B.II.b.3.d)
Change Requirement
• Change in the manufacturing process of the finished
product, including an intermediate used in the
manufacture of the finished product: Introduction of a
non-standard terminal sterilisation method
For critical dosage forms (e.g. suspensions or emulsions
for injection) or when the active substance is known to
be unstable, comparative stability data, 6 months in
duration, long term and accelerated* stability testing
conditions on at least three primary batches are
recommended. Two of three batches should be at least
pilot scale; the third batch may be smaller.
27. 4/16/2014 27
Type II Variation . (B.II.b.3.e)
Change Requirement
• Change in the manufacturing process of the finished
product, including an intermediate used in the
manufacture of the finished product: introduction or
increase in the overage that is used for the active
substance
In variations to the manufacturing process of the
finished product, the following approaches may be
considered as acceptable:
If the quality characteristics (e.g. content of active
substance) of the finished product are changed in a way
that stability may be compromised, comparative stability
data are recommended in long term and accelerated*
testing conditions, on the finished product before and
after the change:
For conventional dosage forms (e.g. conventional release
solid dosage form, solutions) and when the active
substance is known to be stable, comparative stability
data, 6 months in duration, long term and accelerated*
testing conditions on at least two batches of at least
pilot scale are recommended.
28. 4/16/2014 28
Type II Variation . (B.II.b.4.d)
Change Requirement
• Change in the batch size (including batch size ranges)
of the finished product: The change relates to all other
pharmaceutical forms manufactured by complex
manufacturing processes
In variations to the batch size of the finished product,
the following approaches may be considered as
acceptable:
If the quality characteristics (e.g. impurity profile) of the
finished product are changed in a way that stability may
be compromised, comparative stability data are
recommended in long term and accelerated* testing
conditions, on the finished product before and after the
change:
For conventional dosage forms manufactured by a
complex manufacturing process and when the active
substance is known to be stable, comparative stability
data, 6 months in duration, long term and accelerated*
testing conditions on at least two batches of at least
pilot scale are recommended.
29. 4/16/2014 29
Type II Variation . (B.II.e.1.a.3)
Change Requirement
• Change in immediate packaging of the finished
product: Qualitative and quantitative composition:
Sterile medicinal products and
biological/immunological medicinal products
In case of a change to the immediate packaging of the
finished product the following approach may be
considered as acceptable:
In the case of less protective packaging or when a risk of
interaction occurs for a sterile medicinal product,
comparative stability data are recommended using long
term and accelerated* testing conditions of six months
in duration on at least three primary batches of the
finished product. Two of three batches should be at least
pilot scale; the third batch may be smaller.
(Note: According to the scope this guideline is not
applicable to biological/immunological active substances
and related finished products).
30. 4/16/2014 30
Type II Variation . (B.II.e.1a.4)
Change Requirement
• Change in immediate packaging of the finished
product: Qualitative and quantitative composition: The
change relates to a less protective pack where there
are associated changes in storage conditions and/or
reduction in shelf life.
In case of a change to the immediate packaging of the
finished product the following approach may be
considered as acceptable:
In the case of less protective packaging or when a risk of
interaction occurs, mainly for semi-solid or liquid
dosage forms, comparative stability data are
recommended using long term and accelerated* testing
conditions of six months in duration on at least three
primary batches of the finished product. Two of three
batches should be at least pilot scale; the third batch
may be smaller.
31. 4/16/2014 31
Type II Variation . (B.II.e.1.b.2)
Change Requirement
• Change in immediate packaging of the finished
product:
• Change in type of container or addition of a new
container: Sterile medicinal products and
biological/immunological medicinal products
In case of a change to the immediate packaging of the
finished product the following approach may be
considered as acceptable:
In the case of less protective packaging or when a risk of
interaction occurs, mainly for semi-solid or liquid
dosage forms, comparative stability data are
recommended using long term and accelerated* testing
conditions of six months in duration on at least three
primary batches of the finished product. Two of three
batches should be at least pilot scale; the third batch
may be smaller.
(Note: According to the scope this guideline is not
applicable to biological/immunological active substances
and related finished products).
32. 4/16/2014 32
Type II Variation . (B.II.e.4.b)
Change Requirement
• Change in shape or dimensions of the container or
closure (immediate packaging):
• The change in shape or dimensions concerns a
fundamental part of the packaging material, which
may have a significant impact on the delivery, use,
safety or stability of the finished product
In variations to the immediate packaging of the finished
product, which may have a significant impact of the
stability of the finished product, the following approach
may be considered as acceptable:
If the quality characteristics (e.g. impurity profile) of the
finished product are changed in a way that stability may
be compromised, comparative stability data are
recommended in long term and accelerated* testing
conditions, on the finished product before and after the
change:
For conventional dosage forms manufactured by a
complex manufacturing process and when the active
substance is known to be stable, comparative stability
data, 6 months in duration, long term and accelerated*
testing conditions on at least two batches of at least
pilot scale are recommended.
33. 4/16/2014 33
Type II Variation . (B.II.e.4.b)
Change Requirement
• Change in shape or dimensions of the container or
closure (immediate packaging):
• The change in shape or dimensions concerns a
fundamental part of the packaging material, which
may have a significant impact on the delivery, use,
safety or stability of the finished product
For critical dosage forms (e.g. modified release form) or
when the active substance is known to be unstable,
comparative stability data, 6 months in duration, long
term and accelerated* stability testing conditions on at
least three primary batches are recommended. Two of
three batches should be at least pilot scale; the third
batch may be smaller.
34. 4/16/2014 34
Type II Variation . (B.II.e.5.c)
Change Requirement
• Change in pack size of the finished product:
• Change in fill weight/fill volume of sterile multidose
(or single-dose) parenteral medicinal product,
including biological/immunological medicinal
products
In case of such a change to the pack size of the finished
product the following approach may be considered as
acceptable:
If the quality characteristics (e.g. impurity profile) of the
finished product are changed in a way that stability may
be compromised, comparative stability data are
recommended in long term and accelerated* testing
conditions, on the finished product before and after the
change:
Comparative stability data are recommended using long
term and accelerated* testing conditions of six months
in duration on at least three primary batches of the
finished product. Two of three batches should be at least
pilot scale; the third batch may be smaller.
(Note: According to the scope this guideline is not
applicable to biological/immunological active substances
and related finished products).
35. This presentation was compiled from freely
available resources like the website of EMA
specifically “Guideline on stability testing for
applications for variations to a marketing
authorisation”
“Drug Regulations” is a non profit organization
which provides free online resource to the
Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
4/16/2014 35
Drug Regulations : Online
Resource for Latest Information